Inside a Greek temple in Athena, in the era of BC, a priest dressed in white and a long gray beard, flanked by torches on both sides, stood reciting prayers and worshiping "Hygieia", the Greek goddess of health, and before him lay a terrified girl handcuffed The hands and feet, sunken in the eyes, the cheekbones protruding noticeably as a result of malnutrition, and from time to time one of the executioners beats her with a whip.

Despite the severity of the scene, it was not a bloody torture ritual, but rather a healing ritual, in an attempt to expel the demons that possessed that poor girl who only complained that she was sad and feeling empty.

This was the case in the past with many mental illnesses, which were attributed to demonic possession or lack of faith, and priests and clerics were the ones who took care of such cases over several centuries (1).

In fact, this belief is still prevalent to this day in some areas, but with time, everything has evolved, we have known about mental illness after a very long scientific battle, and modern drugs have appeared that have revolutionized the treatment of this type of disease, but one of them has changed The world has been completely transformed for the past thirty years, and a new era has begun, the Prozac era.

Half successful attempts

We can trace the history of depression over the past 2,500 years, from the writings of the Greeks to the most recent edition of the most famous diagnostic books in psychiatry today.

Despite this, the Persian Muslim physician "Abu Bakr al-Razi" in the ninth century AD was probably the first to suggest that mental illnesses, including depression, stem from the mind, and developed what could be considered a primitive form of behavioral therapy.

After the passage of centuries and attempts and failed experiments, depression was treated using opium in the early twentieth century, and despite its promising results, it was quickly rejected due to its susceptibility to addiction (2).

In the fifties, doctors used a drug called “Iproniazid” to treat tuberculosis, and it is a member of the “Monoamine Oxidase Inhibitor” family. Surprisingly, they found that it had side effects represented in opening the appetite, feeling euphoric, activity and improving sleep;

What prompted researchers to try it in the treatment of depression.

Despite the drug's success in treating depression symptoms, its dangerous side effects caused it to be taken off the market once safer alternatives appeared.

But this drug had another benefit, as it enabled researchers to develop the "monoamine hypothesis", according to which the lack of monoamines in the blood, which are neurotransmitters and hormones such as serotonin and dopamine, is the cause of depression, and that was the first building block in The way the drug Prozac appeared on the scene.

In the same period, another drug belonging to the family of "tricyclic antidepressants" appeared called "Imipramine", the first of its kind in this family, which was initially made to treat schizophrenia, but instead showed an improvement in the symptoms of patients severe depression (3).

But then again, his annoying side effects prevented him from dominating the scene.

tri li li

The truth is that the Prozac drug did not see the light overnight, but was the result of research that lasted nearly ten years, among three scientists of the Eli Lilly pharmaceutical company.

Ray Fuller joined the company in 1963 as a pharmacist, and was already interested in research into the treatment of mental illness.

Fuller began his experiments with a group of mice treated with chloramphetamine, which inhibits the production of serotonin in the body, so that he can test different drugs that raise its level again, and then apply it to depressed patients.

He didn't have a plan yet, so he invited fellow organic chemist Bryan Molloy to join his research.

Molly was already working on acetylcholine, but on the heart, and Fuller managed to change his research focus on the brain.

The goal here was to come up with an antidepressant that works exclusively by raising serotonin, without affecting any other hormones or neurotransmitters, to avoid annoying or dangerous side effects.

This was the path that led to the discovery of some of the first antidepressants, and this work continued for several years, until a third member joined the team in 1971.

David Wong introduced a new technology he had heard about in a lecture by a researcher at Johns Hopkins University, who was able to separate some neurons from the brains of mice, and configure them to act exactly like living neurons.

This enabled the trio to directly test the effect of Molly's compounds on neurons, until they found a compound capable of affecting serotonin without affecting almost anything else.

The new compound succeeded in blocking the re-uptake of serotonin into nerve cells.

This means that its effects last for a longer period of time, thus improving symptoms of depression.

Serotonin is secreted from the ends of nerve cells, and floats in the space between them, to perform its functions that revolve around controlling mood, sleep, digestion and sexual desire.

The trio repeated the experiment in Fuller rats treated with "chlor-amphetamine", and the results were similar, and on that happy day, the drug "fluoxetine", the first drug in the group of "serotonin reuptake inhibitors" (SSRIs), which was promoted by the "Lilly" company, was born. Prozac” in 1988, which has become the most popular antidepressant in the world to this day (4).

Planet Prozac

"I think Tess' story contains an undocumented reason for Prozac's immense popularity, which is his ability to change character."

(Peter Kramer - "Listen to Prozac")

In his book "Listening to Prozac", "Peter Kramer" - the American psychiatrist - tells about the patient "Tess" who had a miserable childhood, and became depressed after she failed to marry, although she succeeded in Her career has been quite a success.

After a semi-successful trial with imipramine, Prozac was first introduced to the market, when Kramer decided to give it a try with Tess and watched for the results, which were pretty amazing to them.

Listening to Prozac - Peter Kramer

The first thing Tess noticed, just two weeks after starting the new drug, was that she was feeling energized and energetic, a feeling she had missed almost her whole life. "She laughed more, and the quality of her laugh was different, full of energy," Kramer says.

Not only has her love life improved, but she's also better able to deal with the ongoing work issues that were causing her great anxiety before Prozac.

Kramer believes that this drug not only cured her depression, but also radically changed the way she thinks, her personality, and how she deals with problems, making her a social, cheerful and confident woman.

However, Mrs. Tess' experience was a special case, despite her great fame in the history of this drug, which has already been subject to a lot of criticism, including what the spouses "Peter & Ginger Breggin" mentioned in their book "Talking back to Prozac." "The company that produced Prozac tampered with the course of the study before it was approved by the Food and Drug Administration (FDA) so that the results appeared to be better than they actually are.

The couple attacked not only Prozac, but also all modern antidepressants that appeared later, claiming that major pharmaceutical companies deluded people that they needed this drug;

to increase its sales.

"The secret I sometimes think I'm the only one I know, is that Prozac isn't really that great. Of course I can say this and at the same time believe that Prozac is the miracle that saved my life and got me out of a full-time depression."

(Elizabeth Wertzel - The Prozac Nation)

The Prozac Nation - Elisabeth Wertzel

Was it just a hoax?!

Prozac had sales of $2–3 billion annually around the world, until the patent expiration date in 2001 and the emergence of new competitors (5).

This may make you wonder: Is Prozac really effective?

If we look at the big picture, we can clearly see that rates of depression around the world have not improved since the 1980s to the present day, but rather increased by 50% between 1990 and 2017, despite the prevalence of antidepressants and various psychotherapies (6).

We cannot accuse medicines of total failure if we know that the causes of depression in themselves have increased in recent decades, thanks to the openness of the Internet, economic turmoil and rapid social changes (7).

And if we look in particular at Prozac, as the miracle drug that reached 40 million users worldwide in 2008, the results of the studies are good, but not perfect.

In a study of children ages 7 to 18 with major depression who were treated with fluoxetine, relapse rates were found in children who took fluoxetine to be lower than those who took a placebo.

This means that fluoxetine is effective in protecting against relapse in approximately 60% of cases in children (8).

While another study published in "Dialogues in Clinical Neuroscience" indicates that the recovery rate from a depressive episode does not exceed 40% in the best estimates (9).

There are other reasons that may be related to the nature of the disease itself, or to the social conditions surrounding patients, or the patient’s lack of commitment to treatment, or the sufficiency of drug treatment without the help of psychological treatment, all of these reasons may lead to an exacerbation of the phenomenon of depression in the world, to become one of the biggest diseases contributing to “disability” Disability)” globally, and one of the most important causes of death as well.

The real danger of Prozac and similar antidepressants may lie in that they are over-the-counter drugs, so friends may recommend them to each other after they bring good results with one of them, without consulting the doctor.

It is true that Prozac and the rest of his family may not represent a direct threat to life except in high doses, but this does not mean that it is completely free of side effects, the most famous of which are stomach upset, loss of sexual desire and increased tension in some cases.

In addition, treating depression with medication alone without referring to a specialized psychiatrist may exacerbate the problem later on. Each episode of depression that affects a person leaves an impact on brain cells that makes the next episode more fierce, and more difficult to treat (10).

The other thing is that the new generation of antidepressants, which began with the emergence of Prozac, may cause suicidal tendencies in children and adolescents under the age of 18, in the first weeks of starting treatment, so it is not possible in any case to advise a depressed teenager to take this group of drugs without supervision. Strict medical.

An exception to this is Prozac itself, which was found to be the safest and most effective in children and adolescents, but this does not prevent it from being given under medical supervision as well (11).

On the other hand, the wide fame of Prozac includes within it the supremacy within the scientific community of a theory that says that mental illness is nothing but a disorder in the brain systems that requires chemical intervention only to control it, and the matter is over, but that is not true, as mental illness is so complex that this theory is considered Too reductive, it discourages the scientific community from pursuing adjuvant therapies (such as session psychotherapy) for chemotherapy.

For example, a study was published several years ago in the "International Journal of Epidemiology" (12), conducted by a team from the University of Michigan over a full 12 years, in an attempt to monitor the basic mechanisms underlying bipolar disorder, which affects more than 60 million individuals Around the world, the study found 7 potential roots for bipolar disorder: there are genetic and physiological mechanisms, there are alcohol and smoking addictions, there are problems with cognitive and neurological abilities (thinking, memory, daily functioning), and there are psychological mechanisms (such as antisocial behavior, anxiety, and childhood disorders). There are circadian rhythms and sleep disturbances, there are diets high in saturated fats, and there are eating disorders.

This means, then, that it is more complicated than what scientists thought, and although the most effective treatments for bipolar disorder now (or depression, anxiety, or others) only inhibit or raise the values ​​of chemical transporters in the body, what drives these vectors is still not understood. Clearly, and perhaps needs to combine several different research paradigms, so it is distinguished in this study to find an overlap between researchers from several fields, psychology, genetics, mathematics, engineering...etc.

The discovery of various drugs to treat depression certainly revolutionized the world of psychiatry. After more than two thousand years of using magic, spells and useless treatments, a depressed patient can finally lead a normal life without being accused of insanity or lack of faith.

However, psychiatry still has a very long way to go to reach a full understanding of mental illness, Prozac in the end is not magic described by a fortune-teller!

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Sources:

  • The History of Depression and Treatment

  • Opioids to Treat Depression: The Jury Is Out

  • A brief history of the development o

    f antidepressant drugs: From monoamines to glutamate – PMC

  • Ray W. Fuller, David T. Wong, and Bryan B. Molloy |

    Science History Institute.

  • previous source

  • Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study - ScienceDirect.

  • Depression Millennials Increasing

  • Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents

  • Towards achieving remission in the treatment of depression - PMC.

  • Microglia and major depression: not yet a clear picture

  • Do Antidepressants Increase the Risk of Suicide in Children and Adolescents?

  • Cohort Profile: The Heinz C. Prechter Longitudinal Study of Bipolar Disorder